Acute pulmonary edema and emphysema can be induced in cattle, goats, and sheep with an intraruminal or intravenous dose of 3-methylindole (skatole). Three-methylindole is a ruminal fermentation product of tryptophan which is formed by a, yet to be characterized, Clostridium bacteria. Three-methylindole is rapidly metabolized and as many as 11 metabolites or conjugated end-products are excreted in the urine of several species. Low concentrations of 3-methylindole are associated with the development of pulmonary lesions in ruminants. Intrabronchial infusion of isotonic 3-methylindole solutions can cause pulmonary lesions, including proliferation of alveolar epithelial cells, indicating that 3-methylindole can have a direct effect on the lungs. The mechanism of action of 3-methylindole and sequence of biochemical and morphological changes is being studied with respect to its tissue concentration, possible formation of harmful metabolites, and membrane labilizing effects related to its lipophilicity. Since these parameters can be studied under reproducible experimental conditions, this is a useful animal model for investigation of acute pulmonary damage. In addition, research is being conducted to determine whether 3-methylindole is associated with the development of naturally-occurring acute pulmonary edema and emphysema in cattle. BIBLIOGRAPHIC REFERENCES: Bray, T. M., H. E. Sandberg, and J. R. Carlson. An EPR study of the structural perturbations induced by 3-methylindole in the protein and lipid regions of erythrocyte membranes. Biochim. Biophys. Acta. 382, 534-541, 1975. Bray, T. M., and J. R. Carlson. The effects of 3-methylindole on hemolysis, transport of 22Na, and ATP'ase activities of bovine erythrocytes. Proc. Soc. Exp. Biol. Med. 148, 875-879, 1975.